Near-fatal cocaine intoxication in an infant with thrombotic microangiopathy associated with multiple organ failure / Intoxicação grave por cocaína em criança com microangiopatia trombótica associada à falência múltipla de órgãos

ABSTRACT Objective: To report a pediatric case of drug-induced thrombotic microangiopathy caused by cocaine Case description: We report a nine-month-old patient who developed thrombotic microangiopathies after extreme cocaine intoxication, multiple organ dysfunction syndrome with hemodynamic dysfunction, anuric renal failure, liver failure, encephalopathy, and myocardial injury, corresponding phenotypically to thrombocytopenia-associated multiple organ failure. The patient received continuous venous hemofiltration and therapeutic plasma exchange, recovering satisfactorily. She was discharged after 30 days of hospitalization under the guidance of the childcare service, and was healthy after one year of follow-up. Toxicological samples confirmed high levels of cocaine and derivatives in blood, urine and hair. Comments: To our knowledge, this is the first reported pediatric case. There are particularities of cocaine intoxication pathophysiology that can trigger thrombotic microangiopathies because of vasoconstriction, direct endothelial injury, platelet activation, and increasing von Willebrand factor and fibrinogen levels. All of which results in a prothrombotic state, inflammatory dysregulation, and microvascular thrombi. The increasing use of cocaine, especially among young adults, puts children at high risk of toxicity, either by passive unintentional exposure, or abuse due to the increased availability in homes.

RESUMO Objetivo: Relatar um caso pediátrico de microangiopatia trombótica induzida por drogas causada por cocaína Descrição do caso: Relatamos uma paciente de nove meses de idade que desenvolveu microangiopatia trombótica após intoxicação extrema por cocaína, síndrome de disfunção de múltiplos órgãos com disfunção hemodinâmica, insuficiência renal anúrica, insuficiência hepática, encefalopatia e lesão miocárdica, correspondendo fenotipicamente à falência múltipla de órgãos associada à trombocitopenia. A paciente recebeu hemofiltração venosa contínua e plasmaférese terapêutica, recuperando-se satisfatoriamente. Recebeu alta após 30 dias de internação sob orientação do serviço de puericultura e estava saudável após um ano de seguimento. Amostras toxicológicas confirmaram altos níveis de cocaína e derivados no sangue, urina e cabelos. Comentários: Até onde sabemos, este é o primeiro caso pediátrico relatado. Existem particularidades da fisiopatologia da intoxicação por cocaína que podem desencadear a microangiopatia trombótica devido à vasoconstrição, lesão endotelial direta, ativação plaquetária e aumento do fator de von Willebrand e dos níveis de fibrinogênio. Tudo isso resulta em um estado pró-trombótico, desregulação inflamatória e trombos microvasculares. O uso crescente de cocaína, principalmente entre adultos jovens, coloca as crianças em alto risco de toxicidade, seja por exposição passiva não intencional ou abuso devido à maior disponibilidade nas residências.

Microangiopatías trombóticas en niños críticamente enfermos. Registro español MATUCIP / Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain

Introducción: Las microangiopatías trombóticas (MAT) son entidades infrecuentes que suelen causar afectación renal, hematológica, neurológica y cardiovascular, con síntomas inespecíficos pero graves. Con la finalidad de mejorar el conocimiento de sus características clínicas, el proceso diagnóstico y el tratamiento en la fase aguda, se ha creado el registro de MAT en las unidades de cuidados intensivos pediátricos (UCIP) de España (Registro MATUCIP). Pacientes y métodos: Estudio observacional, multicéntrico, realizado en 20 UCIP españolas desde enero de 2017 hasta diciembre de 2021 que incluyó niños mayores de 1mes con diagnóstico de MAT y seguimiento hasta el alta de la UCIP. Resultados: Se incluyeron 97 pacientes (51,5% mujeres), con una mediana de edad de 2,6años (RIQ: 1,6-5,7). La clínica inicial fue de tipo gastrointestinal (74,2%), respiratoria (14,4%), cuadro febril (5,2%), neurológica (3,1%) y otras (3,1%). Al ingreso, el 75,3% presentaban anemia hemolítica microangiopática, el 95,9% trombocitopenia y el 94,8% daño renal agudo. Fueron diagnosticados de síndrome hemolítico urémico (SHU) asociado a Escherichia coli productora de toxina Shiga el 57,7%, SHU por Streptococcus pneumoniae el 14,4%, SHU atípico el 15,6%, MAT secundaria el 10,3% y púrpura trombótica trombocitopénica el 2,1%. Desarrollaron hipertensión arterial el 89,7%, manifestaciones digestivas el 49,5%, respiratorias el 22,7%, neurológicas el 25,8% y cardiacas el 12,4%. El 60,8% requirieron depuración extrarrenal y el 2,1%, plasmaféresis. Recibieron eculizumab 20 pacientes. La mediana de estancia en la UCIP fue de 8,5días (RIQ: 5-16,5). Dos niños fallecieron. (AU)

Introduction: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. Patients and methods: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1month with TMAs, who were followed up through the discharge from the PICU. Results: The sample included 97 patients (51.5% female) with a median age of 2.6years (interquartile range [IQR]: 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5days (IQR: 5-16.5). Two children died. (AU)

Fallo agudo de ventrículo derecho debido a microangiopatía / Right ventricle failure secondary to thrombotic microangiopathy

La microangiopatía trombótica tumoral pulmonar es una enfermedad infrecuente con un diagnóstico de elevada complejidad,que requiere una alta sospecha clínica. La detección precoz es importante debido al mal pronóstico en estadios avanzados.Presentamos el caso de un varón de 39 años ingresado en el hospital para estudio por tos, disnea progresiva, hipertensiónpulmonar y adenopatías abdominales. Durante su ingreso sufrió parada cardiorrespiratoria que no respondió a maniobrasde reanimación cardiopulmonar avanzadas. El examen post mortem mostró hallazgos compatibles con microangiopatíatrombótica tumoral pulmonar secundaria a adenocarcinoma gástrico en estadio avanzado.(AU)

Pulmonary tumour thrombotic microangiopathy is an infrequent disease with a high complex diagnosis that requires highclinical suspicion. Early detection is important because of the poor prognosis in advanced stages. We introduce a case of a39-year-old male admitted in hospital with symptoms of cough, progressively worsening dyspnea, pulmonary hypertensionand abdominal adenopathies. During admission he suffered a cardiac arrest with no response to advanced cardiopulmonaryresuscitation manoeuvres. Post mortem study revealed a pulmonary tumoral thrombotic microangiopathy secondary to gastricadenocarcinoma in advanced stage.(AU)

Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain.

INTRODUCTION: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP Registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. METHODS: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1 month with TMAs, who were followed up through the discharge from the PICU. RESULTS: The sample included 97 patients (51.5% female) with a median age of 2.6 years (interquartile range [IQR], 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5 days (IQR, 5-16.5). Two children died. CONCLUSIONS: The MATUCIP registry demonstrates the clinical variability of TMA cases requiring admission to the PICU. Knowledge of the presentation and outcomes of TMAs can facilitate early aetiological diagnosis. This registry can help improve our understanding of the clinical spectrum of these diseases, for which there is a dearth of published data.

Immune thrombotic thrombocytopenic purpura: clinical suspicion and basic management in emergency departments - an expert review and consensus statement from the Spanish societies of hematology and hemotherapy (SEHH) and emergency medicine (SEMES). / Púrpura trombocitopénica trombótica inmune: sospecha y manejo básico en los servicios de urgencias. Revisión y consenso de un grupo de expertos de las sociedades científicas SEHH y SEMES.

TEXT: Acquired or immune thrombotic thrombocytopenic purpura (TTP) are thrombotic microangiopathies associated with high mortality if treatment is not started early. Onset is usually sudden, meaning that the condition is often diagnosed in hospital emergency departments, where TTP must be suspected as early as possible. These guidelines were drafted by specialists in emergency medicine and hematology to cover the diagnosis, referral, and treatment of patients suspected of immune-mediated TTP who require emergency care. Immune TTP should be suspected whenever a patient presents with hemolytic microangiopathy and has a negative Coombs test, and thrombocytopenia, possibly in conjunction with fever and neurologic and cardiac alterations. If one of the existing diagnostic algorithms indicates there is a high probability that the patient has immune TTP, plasma exchange therapy should be started along with immunosuppressants. Treatment with caplacizumab should also be considered. The patient should be referred immediately to the hematology department within the same hospital or a referral hospital.

TEXTO: La púrpura trombótica trombocitopénica adquirida o inmune (PTTi) es una microangiopatía trombótica (MAT) con una elevada mortalidad si no se instaura un tratamiento precoz. El inicio habitualmente brusco de la enfermedad hace que, en la mayoría de los pacientes, el diagnóstico inicial se haga en los servicios de urgencias hospitalarios (SUH), donde se debe sospechar esta entidad con la mayor inmediatez posible. Esta guía, elaborada por profesionales de Medicina de Urgencias y de Hematología, establece unas recomendaciones en cuanto al diagnóstico, derivación y tratamiento de los pacientes con sospecha de PTTi en los SUH. Se debe sospechar PTTi en todo paciente que presente una anemia hemolítica microangiopática, prueba de Coombs directo negativa y trombocitopenia pudiendo asociar, además, fiebre, alteraciones neurológicas y cardiacas. Si tras la aplicación de alguno de los algoritmos diagnósticos existentes, hay una alta probabilidad de que el paciente presente una PTTi, debería iniciarse tratamiento con recambio plasmático, inmunosupresores y valorar el inicio de caplacizumab. Además, debe gestionarse el traslado inmediato de los pacientes al Servicio de Hematología, bien del mismo centro o a uno de referencia.

Púrpura trombocitopénica trombótica inmune: sospecha y manejo básico en los servicios de urgencias. Revisión y consenso de un grupo de expertos de las sociedades científicas SEHH y SEMES / Immune thrombotic thrombocytopenic purpura: clinical suspicion and basic management in emergency departments — an expert review and consensus statement from the Spanish societies of hematology and hemotherapy (SEHH) and emergency medicine (SEMES)

La púrpura trombótica trombocitopénica adquirida o inmune (PTTi) es una microangiopatía trombótica (MAT) con una elevada mortalidad si no se instaura un tratamiento precoz. El inicio habitualmente brusco de la enfermedad hace que, en la mayoría de los pacientes, el diagnóstico inicial se haga en los servicios de urgencias hospitalarios (SUH), donde se debe sospechar esta entidad con la mayor inmediatez posible. Esta guía, elaborada por profesionales de Medicina de Urgencias y de Hematología, establece unas recomendaciones en cuanto al diagnóstico, derivación y tratamiento de los pacientes con sospecha de PTTi en los SUH. Se debe sospechar PTTi en todo paciente que presente una anemia hemolítica microangiopática, prueba de Coombs directo negativa y trombocitopenia pudiendo asociar, además, fiebre, alteraciones neurológicas y cardiacas. Si tras la aplicación de alguno de los algoritmos diagnósticos existentes, hay una alta probabilidad de que el paciente presente una PTTi, debería iniciarse tratamiento con recambio plasmático, inmunosupresores y valorar el inicio de caplacizumab. Además, debe gestionarse el traslado inmediato de los pacientes al Servicio de Hematología, bien del mismo centro o a uno de referencia. (AU)

Acquired or immune thrombotic thrombocytopenic purpura (TTP) are thrombotic microangiopathies associated with high mortality if treatment is not started early. Onset is usually sudden, meaning that the condition is often diagnosed in hospital emergency departments, where TTP must be suspected as early as possible. These guidelines were drafted by specialists in emergency medicine and hematology to cover the diagnosis, referral, and treatment of patients suspected of immune-mediated TTP who require emergency care. Immune TTP should be suspected whenever a patient presents with hemolytic microangiopathy and has a negative Coombs test, and thrombocytopenia, possibly in conjunction with fever and neurologic and cardiac alterations. If one of the existing diagnostic algorithms indicates there is a high probability that the patient has immune TTP, plasma exchange therapy should be started along with immunosuppressants. Treatment with caplacizumab should also be considered. The patient should be referred immediately to the hematology department within the same hospital or a referral hospital. (AU)

Síndrome nefrótico como manifestación de microangiopatía trombótica secundaria al uso crónico de sunitinib / Nephrotic syndrome as a manifestation of thrombotic microangiopathy due to long-term use of sunitinib

El síndrome nefrótico en los pacientes con cáncer se puede asociar a su enfermedad de base o al tratamiento quimioterapéutico. El cáncer de órganos sólidos puede producir una glomerulonefritis membranosa que se manifiesta con síndrome nefrótico; otras presentaciones histológicas menos frecuentes son la glomeruloesclerosis focal y segmentaria y la enfermedad de cambios mínimos. Adicionalmente, los tratamientos quimioterapéuticos pueden causar toxicidad renal por afección de los pequeños vasos sanguíneos, los glomérulos, los túbulos y el intersticio. Los inhibidores de la tirosina quinasa como el sunitinib pueden causar daño endotelial y podocitario, produciendo una microangiopatía trombótica limitada a los riñones, que se manifiesta con proteinuria e hipertensión. Se presenta el caso de un hombre anciano con tumor del estroma gastrointestinal (GIST, por sus siglas en inglés) que fue tratado con sunitinib y como complicación presentó una microangiopatía trombótica manifestada con síndrome nefrótico e hipertensión de difícil control, que se controló al suspender este medicamento pero con desenlace fatal por su neoplasia maligna. (AU)

Nephrotic syndrome in patients with cancer may be related to the primary malignancy or chemotherapeutic therapy. Solid organ cancers may cause membranous glomerulonephritis manifesting with nephrotic syndrome; other less common histologic presentations include focal and segmental glomerulosclerosis and minimal change disease. In addition, chemotherapy agents can cause renal toxicity by affecting the small blood vessels, glomeruli, tubules, and interstitium. Tyrosine kinase inhibitors such as sunitinib may cause endothelial and podocyte damage leading to renal limited thrombotic microangiopathy, manifested by proteinuria and hypertension. We report a case of an elderly man with gastrointestinal stromal tumor (GIST) on treatment with sunitinib who had as a complication of a thrombotic microangiopathy manifested with nephrotic syndrome and difficult-to-control hypertension, which was controlled by stopping this drug but with a fatal outcome due to its malignant neoplasm. (AU)

Capilaroscopia, microangiopatía y VIH. Estudio descriptivo de hallazgos capilaroscópicos en pacientes con VIH / Capillaroscopy, microangiopathy, and HIV. Descriptive study of capillaroscopy findings in HIV positive patients

Fundamento: El objetivo de este estudio fue valorar la afectación microangiopática mediante capilaroscopia en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). Apenas ha sido estudiada y podría constituir una herramienta de diagnóstico precoz de afectación cardiovascular en estos pacientes. Material y métodos: Estudio transversal que incluyó pacientes mayores de 18 años, diagnosticados de infección por VIH entre 2008 y 2018. Se recogieron variables demográficas (sexo, edad), analíticas (tiempo de infección, CD4, CD4/CD8, coinfección por otros virus), tratamiento antirretroviral y comorbilidades (tabaquismo, enolismo, hipertensión arterial, dislipemia, diabetes, cardiopatía). Se realizó una capilaroscopia y un análisis de sangre en el mismo acto. Las alteraciones capilaroscópicas evaluadas fueron: congestión, tortuosidades, hemorragias, dilataciones, pérdida capilar y megacapilares. Resultados: Se incluyeron 102 pacientes, 73,5% hombres, edad media 40 años (DE: 10) y tiempo medio de infección 4,5 años (DE: 3,1). Al diagnóstico, la media de CD4 fue 408 células/mm3 y la razón CD4/CD8 fue 0,4. El 14,7% presentaban coinfección por el virus de la hepatitis B, el 31,3% tabaquismo y el 13,7% enolismo. El 93,1% de pacientes mostró alguna alteración capilaroscópica. Se observaron, por orden de frecuencia, congestión (78,5%), tortuosidades (77,5%), hemorragias (13,8%), dilataciones (11,8%), pérdida capilar (5%) y megacapilares (1%). Las torutuosidades se asociaron a edad y tabaquismo, y las hemorragias a edad, CD4, tratamiento antirretroviral, e hipertensión. Conclusiones: Los pacientes con infección por VIH presentan una prevalencia importante de alteraciones capilaroscópicas, principalmente tortuosidades y congestión. Es la primera descripción de áreas de congestión como hallazgo capilaroscópico en este grupo de pacientes.(AU)

Background: In this study, we aim to evaluate microangiopathy in HIV positive patients by using capillaroscopy. To date, few studies have been published on the topic. Capillaroscopy may be a tool for early diagnosis of cardiovascular involvement in this patient population. Methodology: Cross-sectional study with HIV positive patients >18 years. The enrolment period was set from January to June 2018. The following data were collected: demographic (sex, age), laboratory tests (duration of infection, CD4 cell count, CD4:CD8 ratio, coinfection with other viruses), antiretroviral treatment, dyslipidemia, and comorbidities (active smoking, alcoholism, high blood pressure, dyslipidaemia, diabetes, cardiopathy). The capillaroscopy and blood tests were performed simultaneously. The following alterations were evaluated in the capillaroscopy: congestion, tortuosity, haemorrhage, dilations, capillary loss, and presence of megacapillaries. Results: One hundred and two patients were included; 73.5% were male, mean age was 40 years (SD: 10), and mean duration of infection 4.5 years (SD 3.1). At diagnosis, mean CD4 cell count was 408/mm3 and CD4/CD8 ratio 0.4. A number of patients (14.7%) were coinfected with the hepatitis B virus; 31.3% were active smokers and 13.7% alcoholics. Capillaroscopy alterations were found in most study patients (93.1%): congestion (78.5%), tortuosity (77.5%), haemorrhage (13.8%), dilations (11.8%), capillary loss (5%), and megacapillaries (1%). Capillary tortuosity was associated with age and smoking; and haemorrhage with age, CD4, antiretroviral treatment, and hypertension. Conclusion. Prevalence of capillaroscopy alterations is high in HIV positive patients, particularly tortuosity and congestion. To the best of our knowledge, the later alteration has not been previously reported in this group of patients.(AU)

Chronic gemcitabine-induced thrombotic microangiopathy in the kidneys / Microangiopatía trombótica crónica localizada en riñones asociada al uso de gemcitabina

Abstract Thrombotic microangiopathies (TMAs) are characterized by microvascular occlusion secondary to diffuse endothelial damage which produces inflammation, platelet aggregation and red blood cell destruction, causing ischemic injury to the affected organ. They are clinically characterized by Coombs-negative microangiopathic hemolytic anemia, and multiple organ damage (mainly of the kidneys, central nervous system, cardiovascular apparatus and gastrointestinal tract). They may occur systemically or locally, and they have multiple etiologies. In patients with cancer, determining the cause of thrombotic microangiopathy is a great diagnostic challenge, with the most frequent etiologies being active malignant neoplasms, disseminated intravascular coagulation, infections and antineoplastic drugs. We present the clinical case of a patient with unresectable pancreatic adenocarcinoma on chronic gemcitabine treatment, and highlight the importance of suspecting and distinguishing chemotherapy-induced TMAs from neoplasm-induced TMAs, as their prognosis and treatment are very different. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2249).

Resumen Las microangiopatías trombóticas (MAT) se caracterizan por la oclusión microvascular como consecuencia de una lesión endotelial difusa que produce inflamación, agregación plaquetaria y destrucción de glóbulos rojos, causando daño isquémico del órgano afectado. Se caracterizan clínicamente por anemia hemolítica microangiopática, Coombs negativo, daño multiorgánico (principalmente de riñones, sistema nervioso central, aparato cardiovascular y tracto gastrointestinal). Su presentación puede ser sistémica o localizada y sus etiologías son múltiples. En los pacientes con cáncer es un gran reto diagnóstico establecer la causa de la microangiopatía trombótica, siendo las etiologías más frecuentes la neoplasia maligna activa, la coagulación intravascular diseminada, infecciones y medicamentos antineoplásicos. Se presenta el caso clínico de una paciente con adenocarcinoma cáncer de páncreas irresecable, en manejo crónico con gemcitabina y se resalta la importancia de sospechar y distinguir la MAT inducida por quimioterapia, de la causada por la neoplasia ya que el pronóstico y tratamiento son muy diferentes. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2249).

Recomendaciones para el abordaje clínico de pacientes con púrpura trombocitopénica trombótica / Recommendations for the diagnosis and treatment of patients with thrombotic thrombocytopenic purpura

La púrpura trombocitopénica trombótica (PTT) es una microangiopatía trombótica (MAT) caracterizada por el desarrollo de anemia hemolítica microangiopática, trombocitopenia y disfunción orgánica isquémica asociada a niveles de ADAMTS13 inferiores al 10% en la mayoría de los casos.Recientemente se han producido numerosos avances en el campo de la PTT. Se han desarrollado nuevas técnicas rápidas y accesibles capaces de cuantificar los niveles de ADAMTS13 y los posibles inhibidores. Los sistemas de secuenciación masiva del gen ADAMTS13 facilitan la identificación de polimorfismos en este gen. Además, han aparecido nuevos fármacos como caplacizumab y se plantean estrategias de prevención de recaídas con el uso de rituximab.Los registros de pacientes con PTT permiten ahondar en el conocimiento de esta enfermedad, pero la gran variabilidad en el diagnóstico y tratamiento hace necesaria la elaboración de un documento que homogenice la terminología y la práctica clínica.Las recomendaciones recogidas en el presente documento se han elaborado siguiendo la metodología AGREE. Las preguntas de investigación se formularon de acuerdo con el formato PICO. Se realizó una búsqueda bibliográfica de la literatura publicada durante los últimos 10 años. Las recomendaciones se establecieron por consenso entre todo el grupo puntualizando las fortalezas y limitaciones existentes de acuerdo al nivel de evidencia obtenido.En conclusión, en el presente documento se recogen recomendaciones sobre el tratamiento, diagnóstico y tratamiento de la PTT con el objetivo final de elaborar pautas basadas en la evidencia publicada hasta la fecha que permitan a los profesionales sanitarios optimizar el tratamiento de la PTT. (AU)

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized by the development of microangiopathic haemolytic anaemia, thrombocytopenia, and ischaemic organ dysfunction associated with ADAMTS13 levels lower than 10% in most cases.Recently there have been numerous advances in the field of PTT, new, rapid and accessible techniques capable of quantifying ADAMTS13 activity and inhibitors. The massive sequencing systems facilitate the identification of polymorphisms in the ADAMTS13 gene. In addition, new drugs such as caplacizumab have appeared and relapse prevention strategies are being proposed with the use of rituximab.The existence of TTP patient registries allow a deeper understanding of this disease but the great variability in the diagnosis and treatment makes it necessary to elaborate guidelines that homogenize terminology and clinical practice.The recommendations set out in this document were prepared following the AGREE methodology. The research questions were formulated according to the PICO format. A search of the literature published during the last 10 years was carried out. The recommendations were established by consensus among the entire group, specifying the existing strengths and limitations according to the level of evidence obtained.In conclusion, this document contains recommendations on the management, diagnosis, and treatment of TTP with the ultimate objective of developing guidelines based on the evidence published to date that allow healthcare professionals to optimize TTP treatment. (AU)

Management of atypical uremic hemolytic syndrome in pregnant patient.

Atypical uremic haemolytic syndrome is a variant of thrombotic micro-andiopathy characterized by non-autoimmune hemolytic anemia, thrombocytopenia and acute renal failure as a result of excessive activation of the complement. Up to 60% of patients have mutations in the genes that encode the complement system. A disensing factor is required for its manifestation, including gestation. It is an entity with a high morbidity, which can decrease drastically if an early diagnosis is made and appropriate treatment is initiated. Administration of ecuilizumab has demonstrated rapid process disruption, reducing the need for extrarenal purification therapies and improving renal function and patient prognosis.

Manejo de síndrome hemolítico urémico atípico en la paciente gestante / Management of atypical uremic hemolytic syndrome in pregnant patient

El síndrome hemolítico urémico atípico es una variante de la microangiopatía trombótica caracterizada por presentar anemia hemolítica no autoinmune, trombocitopenia y fallo renal agudo como consecuencia de una excesiva activación del Sistema del complemento. Hasta en un 60% de los pacientes presentan mutaciones en los genes que codifican el sistema del complemento. Se requiere un factor desencadenante para su manifestación, entre los que se encuentra la gestación. Es una entidad que presenta una elevada morbimortalidad, que puede disminuir de forma relevante si se realiza un diagnóstico precoz y se inicia tratamiento adecuado. La administración de eculizumab ha demostrado la interrupción rápida del proceso, con reducción de la necesidad de terapias de depuración extrarrenal y mejoría de la función renal y pronóstico de las pacientes.(AU)

Atypical uremic haemolytic syndrome is a variant of thrombotic micro-andiopathy characterized by non-autoimmune hemolytic anemia, thrombocytopenia and acute renal failure as a result of excessive activation of the complement. Up to 60% of patients have mutations in the genes that encode the complement system. A disensing factor is required for its manifestation, including gestation. It is an entity with a high morbidity, which can decrease drastically if an early diagnosis is made and appropriate treatment is initiated. Administration of ecuilizumab has demonstrated rapid process disruption, reducing the need for extrarenal purification therapies and improving renal function and patient prognosis.(AU)

Índice trabecular óseo y niveles de 25-hidroxivitamina D en las complicaciones microvasculares de la diabetes mellitus tipo 2 / Trabecular bone score and 25-hydroxyvitamin D levels in microvascular complications of type 2 diabetes mellitus

Antecedentes y objetivo:La enfermedad microvascular (EMV) diabética ha sido asociada con una fragilidad ósea incrementada. El objetivo fue analizar la relación entre la EMV y la microestructura trabecular -evaluada mediante el índice trabecular óseo (trabecular bone score, TBS)- en pacientes diabéticos tipo 2 (DM2). Adicionalmente, conocer la relación entre la vitamina D y la EMV.Pacientes y métodos:Diseño transversal analítico, que incluyó varones > 50 años y mujeres postmenopáusicas con DM2, participantes en una cohorte poblacional. Se clasificó como EMV+ la presencia de nefropatía, neuropatía y/o retinopatía. Fueron analizadas variables clínicas, de laboratorio, el TBS, la 25-hidroxivitamina D [25(OH)D] y la densidad mineral ósea (DMO). Se realizaron análisis bivariable y multivariable.Resultados:Fueron evaluados 361 pacientes (51,1% mujeres), de 63,8 (9) años. De ellos, 92 tenían EMV, con un peor control metabólico, mayor duración de la DM2, menor TBS (1,235 [0,1] vs. 1,287 [0,1]; p=0,003) y menores niveles de 25(OH)D (18,3 [7] vs. 21,6 [8] ng/mL; p=0,0001). No hubo diferencias entre EMV+ y EMV- en la DMO ni en los marcadores P1NP y β-CTX. Tras ajustar por confusores, incluyendo HbA1c y duración de la DM2, el TBS en EMV+ fue 1,252 (IC 95% 1,230-1,274) vs. 1,281 (IC 95% 1,267-1,295) en EMV- (p=0,034). La EMV se asoció a un nivel de 25(OH)D < 20 ng/mL con una OR ajustada=1,88 (IC 95% 1,06-3,31; p=0,028).Conclusiones:Los pacientes con EMV presentaron un TBS significativamente menor, tras ajustar por confusores. El análisis multivariable mostró asimismo una asociación significativa entre un nivel bajo de 25(OH)D y la EMV prevalente. (AU)

Background and objective:Diabetic microvascular disease (MVD) has been associated with increased bone fragility. The objective was to analyse the relationship between MVD and trabecular microstructure -assessed by the trabecular bone score (TBS)- in type 2 diabetic (T2D) patients. A second aim was to know the relationship between vitamin D and MVD.Patients and methods:Cross-sectional study, which included men >50 years and postmenopausal women participating in a population-based cohort, diagnosed with T2D. The presence of nephropathy, neuropathy and/or retinopathy was classified as MVD+. Clinical and laboratory variables, TBS, 25(OH)D and BMD by DXA, were evaluated. Bivariate and multivariate analysis were performed.Results:We evaluated 361 patients (51.1% women), 63.8 (9) years old. Of them, 92 were MVD+ and presented poorer metabolic control, longer duration of T2D, lower TBS [1.235 (.1) vs. 1.287 (.1); p=.007] and lower levels of 25(OH)D [18.3 (7) vs. 21.6 (8) ng/ml; p=.0001). There were no differences between MVD+ and MVD- with regard to BMD or P1NP and β-CTX markers. After adjusting for confounders, including HbA1c and duration of T2D, the TBS value in MVD+ was 1.252 (95% CI 1.230-1.274) vs. 1.281 (95% CI 1.267-1.295) in MVD- (p=.034). MVD was associated with a 25(OH)D level <20 ng ml with an adjusted OR of 1.88 (95% CI 1.06-3.31; p=.028).Conclusions:The MVD+ patients presented a significantly lower TBS, after adjusting for confounders. Furthermore, multivariable analysis showed a significant relationship between a low 25(OH)D level and a prevalent MVD. (AU)

Diagnostic-therapeutic algorithm for thrombotic microangiopathy. A report of two cases.

Thrombotic microangiopathies (TMA) are a group of clinical syndromes associated with haemolytic anaemia, thrombocytopenia and organ dysfunction, mainly renal or neurological. They are associated with significant morbidity and mortality, so early diagnosis and treatment are essential. In this article we report two cases of TMA; a patient with thrombotic thrombocytopenic purpura (TTP) and a patient with atypical haemolytic uraemic syndrome (aHUS).

Algoritmo diagnóstico-terapéutico de las microangiopatías trombóticas. A propósito de 2 casos / Diagnostic-therapeutic algorithm for thrombotic microangiopathy. A report of two cases

Las microangiopatías trombóticas (MAT) son un conjunto de síndromes clínicos que asocian anemia hemolítica, trombocitopenia y disfunción orgánica, principalmente renal o neurológica. Están asociados a una morbimortalidad significativa, por lo que su diagnóstico y tratamiento precoz son esenciales. En este artículo detallamos 2 casos de MAT; una paciente con una púrpura trombocitopénica trombótica (PTT) y otra paciente con un síndrome hemolítico urémico atípico (SHUa).(AU)

Thrombotic microangiopathies (TMA) are a group of clinical syndromes associated with haemolytic anaemia, thrombocytopenia and organ dysfunction, mainly renal or neurological. They are associated with significant morbidity and mortality, so early diagnosis and treatment are essential. In this article we report two cases of TMA; a patient with thrombotic thrombocytopenic purpura (TTP) and a patient with atypical haemolytic uraemic syndrome (aHUS).(AU)

Nephrotic syndrome as a manifestation of thrombotic microangiopathy due to long-term use of sunitinib.

Nephrotic syndrome in patients with cancer may be related to the primary malignancy or chemotherapeutic therapy. Solid organ cancers may cause membranous glomerulonephritis which is manifested by nephrotic syndrome; other less common histologic presentations include focal and segmental glomerulosclerosis and minimal change disease. In addition, chemotherapy agents may cause renal toxicity by affecting the small blood vessels, glomeruli, tubules, and interstitium. Tyrosine kinase inhibitors such as sunitinib may cause endothelial and podocyte damage leading to thrombotic microangiopathy affecting only the kidney and manifested by proteinuria and hypertension. We report a case of an elderly man with gastrointestinal stromal tumor (GIST) on treatment with sunitinib who had as a complication a thrombotic microangiopathy manifested with nephrotic syndrome and a hypertension of difficult control, which was finally controlled by stopping this drug but had a fatal outcome due to its malignancy.

Recommendations for the diagnosis and treatment of patients with thrombotic thrombocytopenic purpura. / Recomendaciones para el abordaje clínico de pacientes con púrpura trombocitopénica trombótica.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized by the development of microangiopathic haemolytic anaemia, thrombocytopenia, and ischaemic organ dysfunction associated with ADAMTS13 levels lower than 10% in most cases. Recently there have been numerous advances in the field of PTT, new, rapid and accessible techniques capable of quantifying ADAMTS13 activity and inhibitors. The massive sequencing systems facilitate the identification of polymorphisms in the ADAMTS13 gene. In addition, new drugs such as caplacizumab have appeared and relapse prevention strategies are being proposed with the use of rituximab. The existence of TTP patient registries allow a deeper understanding of this disease but the great variability in the diagnosis and treatment makes it necessary to elaborate guidelines that homogenize terminology and clinical practice. The recommendations set out in this document were prepared following the AGREE methodology. The research questions were formulated according to the PICO format. A search of the literature published during the last 10 years was carried out. The recommendations were established by consensus among the entire group, specifying the existing strengths and limitations according to the level of evidence obtained. In conclusion, this document contains recommendations on the management, diagnosis, and treatment of TTP with the ultimate objective of developing guidelines based on the evidence published to date that allow healthcare professionals to optimize TTP treatment.

Trabecular bone score and 25-hydroxyvitamin D levels in microvascular complications of type 2 diabetes mellitus. / Índice trabecular óseo y niveles de 25-hidroxivitamina D en las complicaciones microvasculares de la diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Diabetic microvascular disease (MVD) has been associated with increased bone fragility. The objective was to analyse the relationship between MVD and trabecular microstructure -assessed by the trabecular bone score (TBS)- in type 2 diabetic (T2D) patients. A second aim was to know the relationship between vitamin D and MVD. PATIENTS AND METHODS: Cross-sectional study, which included men >50 years and postmenopausal women participating in a population-based cohort, diagnosed with T2D. The presence of nephropathy, neuropathy and/or retinopathy was classified as MVD+. Clinical and laboratory variables, TBS, 25(OH)D and BMD by DXA, were evaluated. Bivariate and multivariate analysis were performed. RESULTS: We evaluated 361 patients (51.1% women), 63.8 (9) years old. Of them, 92 were MVD+ and presented poorer metabolic control, longer duration of T2D, lower TBS [1.235 (.1) vs. 1.287 (.1); p=.007] and lower levels of 25(OH)D [18.3 (7) vs. 21.6 (8) ng/ml; p=.0001). There were no differences between MVD+ and MVD- with regard to BMD or P1NP and ß-CTX markers. After adjusting for confounders, including HbA1c and duration of T2D, the TBS value in MVD+ was 1.252 (95% CI 1.230-1.274) vs. 1.281 (95% CI 1.267-1.295) in MVD- (p=.034). MVD was associated with a 25(OH)D level <20 ng ml with an adjusted OR of 1.88 (95% CI 1.06-3.31; p=.028). CONCLUSIONS: The MVD+ patients presented a significantly lower TBS, after adjusting for confounders. Furthermore, multivariable analysis showed a significant relationship between a low 25(OH)D level and a prevalent MVD.

Brote de 4 casos leptospirosis de un grupo familiar en zona rural tropical de Colombia: un reporte de caso / Outbreak of 4 leptospirosis cases in a family group in tropical rural zone of Colombia: a case report

La leptospirosis es una zoonosis con manifestaciones clínicas causadas por espiroquetas patógenas del género Leptospira spp. Su curso puede ser desde enfermedad leve hasta un síndrome ictero-hemorrágico severo denominado enfermedad de Weil. Se estudió un brote epidemiológico constituido por una serie de cuatro casos de leptospirosis de severidad moderada a severa, ocurridos en una zona rural de clima tropical en los llanos orientales de Colombia, a 450 metros sobre el nivel del mar en una familia visitante en Puerto Lleras, Meta, Colombia. Probablemente secundario al consumo de aguas contaminadas por orina de roedores. Las pacientes fueron ingresadas bajo la sospecha de un síndrome ictérico de origen infeccioso con un falso positivo para antígeno de superficie de hepatitis B. Dos pacientes desarrollaron síndrome de Weil asociado a microangiopatía trombótica por lo que requirieron manejo en unidad de cuidados intensivos (UCI) sin embargo, una de ellas fallece y las otras dos pacientes desarrollan signos y síntomas moderados evidenciando un curso variable de la enfermedad. En nuestro país existe una sobre notificación de síndromes febriles, ictéricos e icterohemorragicos de diferentes etiologías y difícil diagnóstico por lo que la leptospirosis tiende a ser confundida o ignorada como diferencial en muchos casos.

Leptospirosis is a zoonosis with clinical manifestations caused by pathogenic spirochetes of the genus Leptospira spp. Its course can range from mild illness to a severe jaundice-hemorrhagic syndrome called Weil's disease. An epidemiological outbreak consisting of a series of four cases of leptospirosis of moderate to severe severity, which occurred in a rural area with a tropical climate in the eastern plains of Colombia, at 450 meters above sea level, was studied in a visiting family in Puerto Lleras, Meta, Colombia. Probably secondary to the consumption of water contaminated by rodent urine. The patients were admitted on suspicion of an infectious jaundice syndrome with a false positive for hepatitis B surface antigen. Two patients developed Weil's syndrome associated with thrombotic microangiopathy, requiring ICU management, however, one of them died and the other two patients develop moderate signs and symptoms showing a variable course of the disease. In our country there is an overreporting of febrile, jaundice and jaundice syndromes of different etiologies and difficult diagnosis, so that leptospirosis tends to be confused or ignored as differential in many cases.

Gangrena simétrica periférica en los pacientes con infección por SARS-CoV-2 / Peripheral symmetric gangrena in patients with SARS-CoV-2 infection

Introducción:la infección por COVID-19, aunque principalmente con afectación respiratoria, ha puesto de manifiesto diversas manifestaciones clínicas a nivel extrapulmonar. La afectación vascular es frecuente en la unidad de cuidados intensivos aunque su fisiopatología no está del todo clara a día de hoy.Caso clínico:presentamos el caso de un varón de 73 años, con antecedente de crioglobulinemia, ingresado la unidad de cuidados intensivos debido a una neumonía bilateral por COVID-19. Precisó inicio de drogas vasoactivas a dosis bajas, y progresivamente se evidenció isquemia distal de las cuatro extremidades, estableciendo el diagnóstico diferencial entre microangiopatía trombótica o reactivación de la crioglobulinemia.Discusión:la aparición de procesos trombóticos y el riesgo elevado de hemorragia en los pacientes con infección por SARS-CoV-2 ha supuesto uno de los mayores retos en cuanto al tratamiento de esta patología. Las complicaciones vasculares de pequeño vaso, debido en su mayor parte a procesos microangiopáticos distales, han puesto en la palestra el riesgo/beneficio tanto de la anticoagulación, la dosis adecuada, así como su duración.(AU)

Introduction:COVID-19 infection, although mainly with respiratory involvement, has revealed various clinical manifestations at the extrapulmonary level. Vascular involvement is common in the intensive care unit, although its pathophysiology is not clear today.Case report:we present the case of a 73-year-old man, with a history of cryoglobulinemia, admitted to the intensive care unit due to bilateral COVID-19 pneumonia. It required the initiation of vasoactive drugs at low doses, and distal ischemia of the four extremities was progressively evident, establishing the differential diagnosis between thrombotic microangiopathy or reactivation of cryoglobulinemia.Discussion:the appearance of thrombotic processes and the high risk of hemorrhage in patients with SARS-CoV-2 infection has been one of the greatest challenges regarding the treatment of this pathology. Small-vessel vascular complications, mostly due to distal microangiopathic processes, have brought to the fore the risk / benefit of anticoagulation, the appropriate dose, and its duration.(AU)